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. 2018 Jun;6(1-2):45-49.
doi: 10.1166/msr.2018.1073.

The Making and Breaking of Inositol 1,4,5-Trisphosphate Receptor Tetramers

Richard J H Wojcikiewicz  1
Affiliations

The Making and Breaking of Inositol 1,4,5-Trisphosphate Receptor Tetramers

Richard J H Wojcikiewicz. Messenger (Los Angel). 2018 Jun.

Abstract

Mammalian cells express three highly conserved inositol 1,4,5-trisphosphate (IP3) receptor types (IP3R1, IP3R2 and IP3R3), which have broadly similar characteristics, but markedly different distributions, and form homo- or heterotetrameric Ca2+ channels in endoplasmic reticulum (ER) membranes. A vast array of published work details how mature, ER membrane-located IP3 receptor tetramers are regulated, but much less attention has been paid to the intriguing questions of how the tetramers are assembled and destroyed as part of their natural life cycle. Are they assembled at the ER membrane from nascent, or completely translated polypeptides? How are they disassembled and degraded? These questions and other recently defined modes of IP3 receptor processing will be briefly reviewed.

Keywords: Calcium; IP3 Receptor; Ion Channel; Proteasome; Tetramer; Ubiquitin.

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Figures

Figure 1.
Figure 1.
The key elements of tIP3R ERAD. An tIP3R is shown in the process of being targeted by an erlin1/2 complex (dark gray) and constitutively bound RNF170 (red, with the critical RING domain gold). Only 2 of the 4 subunits of the tIP3R are depicted (colored green and red); each is ~2,700 amino acids in length and has 6 TM regions. RNF170 catalyzes tIP3R ubiquitination, resulting in the attachment of homogenous chains of K48- or K63-linked ubiquitin (red ellipses) to cytosolic regions of tIP3R (Wright and Wojcikiewicz, 2016). These chains are recognized by the p97/Ufd1/Npl4 complex that facilitates the transfer of proteins to the proteasome for degradation. Note that the structure shown is of an inactive (closed) tIP3R and that the conformational changes that elicit channel opening, and presumably trigger the association of the erlin1/2 complex-RNF170 module with tIP3R, have yet to be defined.
See this image and copyright information in PMC

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